In the treatment of cancers, particularly where porphine related compounds are used, combined use of laser beam with porphrine cobalt belonging to porphines derived from hemoglobin, mercury compounds, etc. or hematoporphyrin are being studied for practical use. However, the process for preparing these porphin compounds involves prolonged steps since animal blood (hemoglobin) which is limited in supply is processed first to obtain hemin, which is then converted to protoporphyrin. The supply of animal blood as the raw material is unstable, and it is extremely difficult to obtain protoporphyrin and hematoporphyrin derived from protoporphyrin with high purity. See Tetsuro CHO et al, Porphin no Kagaku, p. 47 Kyoritsu Shuppan, 1982.
The present inventors have long been engaged in the study of chlorophyll related compounds and applied for patent right on a highly economical process for separating and purifying pheophorbide in larger quantities which involves simple and brief operations and utilizes as the raw material photo-synthesized organisms that are available in stable supply at low cost. Japanese Laid-Open Patent Application Ser. No. 58-69884, filed Oct. 21, 1981.
On the hypothesis that phorbine compounds prepared from this pheophorbide have more intense physiological activities than porphines mentioned above, the present inventors continued their study and found for the first time that 9-desoxo-9-hydroxy-pheophorbide derivatives and their alkaline salts which are reduced products of pheophorbide (hereinafter referred to as the compounds of the present invention) have excellent pharmacological properties such as marked affinity to cancerous tissues, high photo-sensitivity and destructive effect on cancerous tissues that are superior to those observed in the above-identified porphines.
It has heretofore been known that porphine derivatives of hemoglobin origin are likely to be conjugated with cancerous tissues and are photo-sensitive. However, it has not been realized that phorbine derivatives of chlorophyll have similar physiological activities. In view of the circumstances, the inventors tried to synthesize various compounds from phorbine derivatives of chlorophyll, and after conducting screening tests on these substances, found that the compounds of the invention have pharmacological properties corresponding to those of porphine derivatives of hemoglobin, and thus succeeded in obtaining inexpensive and stable therapeutic agents for cancer to replace expensive and unstable porphines. It has also been discovered that acetyl derivatives of the present compounds in the form of their water soluble alkaline salts were gradually deacetylated in the aqueous solution to be released to 9-desoxo-9-hydroxy-pheophorbide exhibiting the pharmacological properties described above.